March 2021

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Abbasi B, Rizzo JF. Advances in Neuroscience, Not Devices, Will Determine the Effectiveness of Visual Prostheses. Semin Ophthalmol 2021;:1-8.Abstract
Innovations in engineering and neuroscience have enabled the development of sophisticated visual prosthetic devices. In clinical trials, these devices have provided visual acuities as high as 20/460, enabled coarse navigation, and even allowed for reading of short words. However, long-term commercial viability arguably rests on attaining even better vision and more definitive improvements in tasks of daily living and quality of life. Here we review technological and biological obstacles in the implementation of visual prosthetics. Research in the visual prosthetic field has tackled significant technical challenges, including biocompatibility, signal spread through neural tissue, and inadvertent activation of passing axons; however, significant gaps in knowledge remain in the realm of neuroscience, including the neural code of vision and visual plasticity. We assert that further optimization of prosthetic devices alone will not provide markedly improved visual outcomes without significant advances in our understanding of neuroscience.
Aboobakar IF, Friedman DS. Home Monitoring for Glaucoma: Current Applications and Future Directions. Semin Ophthalmol 2021;:1-5.Abstract
Technological advances provide a number of options for glaucoma monitoring outside the office setting, including home-based tonometry and perimetry. This has the potential to revolutionize management of this chronic disease, improve access to care, and enhance patient engagement. Here, we provide an overview of existing technologies for home-based glaucoma monitoring. We also discuss areas for future research and the potential applications of these technologies to telemedicine, which has been brought to the forefront during the ongoing COVID-19 pandemic.
Armstrong GW, Kalra G, De Arrigunaga S, Friedman DS, Lorch AC. Anterior Segment Imaging Devices in Ophthalmic Telemedicine. Semin Ophthalmol 2021;:1-8.Abstract
Obtaining a clear assessment of the anterior segment is critical for disease diagnosis and management in ophthalmic telemedicine. The anterior segment can be imaged with slit lamp cameras, robotic remote controlled slit lamps, cell phones, cell phone adapters, digital cameras, and webcams, all of which can enable remote care. The ability of these devices to identify various ophthalmic diseases has been studied, including cataracts, as well as abnormalities of the ocular adnexa, cornea, and anterior chamber. This article reviews the current state of anterior segment imaging for the purpose of ophthalmic telemedical care.
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Baker TL, Greiner JV, Vesonder M. SARS-CoV-2 safety: Guidelines for shielding frontline nurses. Nursing 2021;51(3):32-42.Abstract
ABSTRACT: Protecting nurses in healthcare facilities from SARS-CoV-2 infection is essential for maintaining an adequate nursing force. Foundational guidelines, consistently utilized, protect the nursing staff from infection. This article describes guidelines designed to reduce acute infection and associated morbidity and mortality among nursing staff and improve compliance with infection prevention protocols.
Baumal CR, Sarraf D, Bryant T, Gui W, Muakkassa N, Pichi F, Querques G, Choudhry N, Teke MY, Govetto A, Invernizzi A, Eliott D, Gaudric A, Cunha de Souza E, Naysan J, Lembo A, Lee GC, Freund BK. Henle fibre layer haemorrhage: clinical features and pathogenesis. Br J Ophthalmol 2021;105(3):374-380.Abstract
BACKGROUND: To describe the clinical presentation and characteristic imaging features of deep retinal haemorrhages primarily located in the Henle fibre layer (HFL) of the macula. The spectrum of aetiologies and a comprehensive theory of pathogenesis are presented. METHODS: This is a retrospective, multicentre case series evaluating eyes with retinal haemorrhage in HFL. Clinical features, underlying aetiology, systemic and ocular risk factors, visual acuity, and multimodal imaging including fundus photography and cross-sectional and en face optical coherence tomography (OCT) are presented. RESULTS: Retinal haemorrhages localised to HFL in 33 eyes from 23 patients were secondary to acute blunt trauma to the head (n=2), eye (n=1) and trunk (n=1), ruptured intracranial aneurysm (Terson's syndrome, n=3), general anaesthesia (n=1), epidural anaesthesia (n=1), hypertension with anaemia (n=1), decompression retinopathy (n=1), postvitrectomy with intraocular gas (n=1), retinal vein occlusion (n=7), myopic degeneration (n=2), macular telangiectasia type 2 (n=1), and polypoidal choroidal vasculopathy (n=1). Defining clinical features included deep retinal haemorrhage with feathery margin and petaloid pattern radiating from the fovea. OCT demonstrated characteristic hyper-reflectivity from the haemorrhage delineated by obliquely oriented fibres in the Henle layer. Spontaneous resolution of HFL haemorrhage occurred after 3 months in 15 patients with follow-up. CONCLUSION: The characteristic petaloid-shaped, deep intraretinal haemorrhage with a feathery margin localised to HFL is associated with various disorders. The terminology 'Henle fiber layer hemorrhage (HH)' is proposed to describe the clinical and OCT findings, which may result from abnormal retinal venous pressure from systemic or local retinovascular disorders affecting the deep capillary plexus or from choroidal vascular abnormalities.
Böhm MS, Wylegala A, Leon P, Ong Tone S, Ciolino JB, Jurkunas UV. One-Year Clinical Outcomes of Preloaded Descemet Membrane Endothelial Keratoplasty Versus Non-Preloaded Descemet Membrane Endothelial Keratoplasty. Cornea 2021;40(3):311-319.Abstract
PURPOSE: To compare the one-year outcomes of preloaded Descemet membrane endothelial keratoplasty (pDMEK) and non-preloaded DMEK (n-pDMEK) in patients with Fuchs endothelial corneal dystrophy (FECD). METHODS: This retrospective comparative cohort study consecutively included 68 eyes with Fuchs endothelial corneal dystrophy who underwent either pDMEK (n = 38) or n-pDMEK (n = 30) performed by cornea fellows with an experienced surgeon between 2016 and 2018 at the Massachusetts Eye and Ear Infirmary. Exclusion criteria were previous surgery (other than uncomplicated cataract surgery) and any documented evidence of macular or other corneal diseases. Corrected distance visual acuity (CDVA), central corneal thickness, intraocular pressure, patient characteristics, postprocessing endothelial cell count, donor graft data, and complications were compared. RESULTS: CDVA showed similar results for pDMEK (0.12 ± 0.11 logarithm of the minimal angle of resolution [LogMAR]) and n-pDMEK (0.13 ± 0.13 LogMAR) (P = 0.827). Sixty-six percent of the pDMEK eyes and 57% of the n-pDMEK eyes achieved a VA of ≥0.1 LogMAR, and 95% and 97%, respectively, achieved a CDVA ≥0.3 LogMAR. The preoperative central corneal thickness of pDMEK and n-pDMEK (644 ± 62.2 μm, 660.5 ± 56.2 μm) decreased significantly after surgery (525.1 ± 43.6 μm, 526.5 ± 45.2 μm, P < 0.001), with no difference between groups (P = 0.840). The postprocessing endothelial cell count did not differ between pDMEK (2959.2 ± 182.9 cells/mm2) and n-pDMEK (2939.3 ± 278.7 cells/mm2) (P = 0.484). Complication rates were comparable with just the rebubbling performed in a minor procedure room showing a lower rate for pDMEK (13.16%) compared with n-pDMEK (33.33%) (P < 0.045). CONCLUSIONS: One-year clinical outcomes were similar between pDMEK and n-pDMEK procedures, rendering eye bank-prepared pDMEK tissues a useful tool in the treatment of endothelial dysfunction.
Braithwaite T, Adderley NJ, Subramanian A, Galloway J, Kempen JH, Gokhale K, Cope AP, Dick AD, Nirantharakumar K, Denniston AK. Epidemiology of scleritis in the United Kingdom from 1997 to 2018: Population-based analysis of 11 million patients and association between scleritis and infectious and immune-mediated inflammatory disease. Arthritis Rheumatol 2021;Abstract
OBJECTIVE: To estimate 22-year trends in scleritis prevalence and incidence and associations with infectious/immune-mediated inflammatory diseases (I-IMIDs) in the United Kingdom (UK). METHODS: Retrospective cross-sectional and population cohort study (1997-2018) included 10,939,823 patients (n=2946 incident scleritis cases) in The Health Improvement Network (THIN), a nationally-representative primary care records database. Case-control and cohort study (1995-2019) included 3005 incident scleritis cases and 12,020 control patients matched by age, sex, region and Townsend Deprivation Index (TDI). We adjusted Poisson, Logistic and Cox proportional hazard multivariable models by age, sex, TDI, race/ethnicity, smoking, nation and body mass index category. Estimates include 95% confidence intervals. RESULTS: Scleritis incidence rates declined from 4·23(2·16-6·31) to 2·79(2·19-3·39) per 100,000 person-years between 1997 and 2018. Prevalence was 93·62(90·17-97·07)/100,000 people in 2018 (61,650 UK patients). Amongst 2946 incident scleritis patients, 62·2%(n=1831) were female, mean age was 44·9(SD17·6, range 1-93) years and 88·8%(n=1257) were White. Higher risk of incident scleritis was associated with female sex (adjusted incidence rate ratio [aIRR]=1·54, 1·43-1·66,p<0.001), Black (aIRR=1·52, 1·14-2·01,p=0.004) or South Asian race/ethnicity (aIRR=1·50, 1·19-1·90,p<0.001) versus White, and older age (peak aIRR=4·95, 3·99-6·14,p<0.001 for ages 51-60 years versus ≤10 years). Compared to controls, scleritis patients had 2-fold increased risk of prior I-IMID diagnosis (p<0.001, 17 I-IMIDs) and significantly increased risk of subsequent diagnosis of 13 I-IMIDs. Strongest associations included granulomatosis with polyangiitis, Behçet's disease, and Sjögren's syndrome. CONCLUSION: Over 1997-2018 the UK incidence of scleritis declined from 4·23 to 2·79/100,000 persons/year. Incident scleritis was associated with 19 I-IMIDs, providing data for rational investigation and cross-specialty engagement.
Brill D, Papaliodis G. Uveitis Specialists Harnessing Disruptive Technology during the COVID-19 Pandemic and Beyond. Semin Ophthalmol 2021;:1-8.Abstract
Spurred by the coronavirus disease pandemic and shortage of eye care providers, telemedicine is transforming the way ophthalmologists care for their patients. Video conferencing, ophthalmic imaging, hybrid visits, intraocular inflammation quantification, and portable technology are evolving areas that may allow more uveitis patients to be evaluated via telemedicine. Despite these promising disruptive technologies, there remain significant technological limitations, legal barriers, variable insurance coverage for virtual visits, and lack of clinical trials for uveitis specialists to embrace telemedicine.
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Caton MT, Zamani AA, Du R, Prasad S. Optic Neuropathy Due to Compression by an Ectatic Internal Carotid Artery Within the Orbital Apex. J Neuroophthalmol 2021;41(1):e103-e104.Abstract
ABSTRACT: Neurovascular compression is a rare but potentially treatable cause of optic neuropathy. Although incidental contact of the cisternal optic nerve and internal carotid artery (ICA) is common, compressive optic neuropathy occurring within the orbital apex has not been comprehensively described. We report a case of intra-orbital and intracanalicular optic nerve compression due to an ectatic ICA in a patient with congenital absence of the contralateral ICA. This report describes the complementary roles of advanced neuroimaging and neuro-ophthalmologic examination in rendering the diagnosis.
Cheng W, Lynn MH, Pundlik S, Almeida C, Luo G, Houston K. A smartphone ocular alignment measurement app in school screening for strabismus. BMC Ophthalmol 2021;21(1):150.Abstract
BACKGROUND: Strabismus is the leading risk factor for amblyopia, which should be early detected for minimized visual impairment. However, traditional school screening for strabismus can be challenged due to several factors, most notably training, mobility and cost. The purpose of our study is to evaluate the feasibility of using a smartphone application in school vision screening for detection of strabismus. METHODS: The beta smartphone application, EyeTurn, can measure ocular misalignment by computerized Hirschberg test. The application was used by a school nurse in a routine vision screening for 133 elementary school children. All app measurements were reviewed by an ophthalmologist to assess the rate of successful measurement and were flagged for in-person verification with prism alternating cover test (PACT) using a 2.4Δ threshold (root mean squared error of the app). A receiver operating characteristic (ROC) curve was used to determine the best sensitivity and specificity for an 8Δ threshold (recommended by AAPOS) with the PACT measurement as ground truth. RESULTS: The nurse obtained at least one successful app measurement for 93% of children (125/133). 40 were flagged for PACT, of which 6 were confirmed to have strabismus, including 4 exotropia (10△, 10△, 14△ and 18△), 1 constant esotropia (25△) and 1 accommodative esotropia (14△). Based on the ROC curve, the optimum threshold for the app to detect strabismus was determined to be 3.0△, with the best sensitivity (83.0%), specificity (76.5%). With this threshold the app would have missed one child with accommodative esotriopia, whereas conventional screening missed 3 cases of intermittent extropia. CONCLUSIONS: Results support feasibility of use of the app by personnel without professional training in routine school screenings to improve detection of strabismus.
Chiou CA, Gragoudas E. Retinal Detachment in a 40-Year-Old Man With Sturge-Weber Syndrome. JAMA Ophthalmol 2021;
Chodnicki KD, Prasad S. Ophthalmic Implications of Chimeric Antigen Receptor T-Cell Therapy. Semin Ophthalmol 2021;:1-6.Abstract
Chimeric antigen receptor (CAR) T-cell therapy is a revolutionary addition to the burgeoning field of immunotherapy. CAR T-cells are engineered by combining a T-cell receptor with the antigen-binding site of an immunoglobulin that allows the hybrid cell to target antigens of interest. CAR T-cell therapy has been approved to treat various hematologic malignancies, including relapsed or refractory B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma. While the treatment efficacy is exciting, challenges remain in understanding the unique spectrum of adverse effects of CAR T-cell therapy, including cytokine release syndrome and neurotoxicity. Innovative research is underway to expand this therapy into solid tumors and fields beyond hematology and oncology. To date, there has been limited research into ophthalmic uses and considerations of CAR T-cell therapy. This review focuses on preclinical investigations into CAR T-cell therapy for retinoblastoma and uveal melanoma, as well as ophthalmic complications of CAR T-cell therapy.
Cohen DA, Gise R, Gaier ED. Serum Biomarkers in Neuro-Ophthalmology: When to Test. Semin Ophthalmol 2021;:1-7.Abstract
Discovery and characterization of serologic biomarkers has revolutionized the diagnostic framework of systemic and paraneoplastic autoimmune neuro-ophthalmic diseases. Expanding recognition of the multiple ocular and visual manifestations of these conditions highlights the important role of the referring provider in identifying potential cases. Increasing ease of access to serologic testing also enables these practitioners to initiate the diagnostic work-up in suspected cases. We aimed to provide an update on the current knowledge surrounding and use of relevant autoimmune biomarkers by correlating specific clinical neuro-ophthalmic manifestations with autoantibody biomarkers. The utility of select biomarkers for myasthenia gravis, neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein-IgG-associated disorder, opsoclonus-myoclonus syndrome, anti-collapsin-response mediator protein-5 optic neuropathy, and glial fibrillary acidic protein-IgG-associated disease are discussed with particular focus on the clinical contexts in which to consider testing.
Collins ME, Guo X, Mudie LI, Slavin RE, Madden N, Chang D, Owoeye J, Repka MX, Friedman DS. Baseline vision results from the Baltimore Reading and Eye Disease Study. Can J Ophthalmol 2021;Abstract
OBJECTIVE: We describe the Baltimore Reading and Eye Disease Study, report baseline ocular findings, and explore the feasibility of eye examinations in the school setting. DESIGN: Prospective, school-based cohort study. PARTICIPANTS: Students in second and third grades. METHODS: Baseline eye examinations, including near and distance presenting visual acuity (VA), stereopsis, ocular alignment, dilated retinal examination, and cycloplegic refraction, were performed in 12 Baltimore public schools during the 2014-15 school year. MAIN OUTCOME MEASURES: Presenting VA, prevalence of refractive error, and other ocular findings. RESULTS: Among the 1054 eligible students, 321 participated. There were 271 (84.4%) African American and 186 (57.9%) female students; mean age was 7.9 ± 0.8 years. Cycloplegia was achieved in 308. The mean presenting distance and near VA was 0.1 ± 0.2 logMAR (range -0.1 to 1.5) and 0.1 ± 0.2 logMAR (range 0.0-1.6) in the better-seeing eye, respectively. The most common ocular findings were +1.00 diopter (D) or greater hyperopia (34.7%), -0.50 D or greater myopia (29.5%), 1.00 D or greater astigmatism (23.4%), and convergence insufficiency (7.2%). Thirty-seven (11.5%) children needed referral to an eye care provider; 10% of students required glasses full-time. CONCLUSIONS: Whereas the majority of second and third grade students in this study have good VA and minimal refractive error, 1 in 9 have an ocular finding necessitating further evaluation. It was feasible to conduct cycloplegic eye examinations in the school setting.
Costela FM, Reeves SM, Woods RL. An implementation of Bubble Magnification did not improve the video comprehension of individuals with central vision loss. Ophthalmic Physiol Opt 2021;Abstract
PURPOSE: People with central vision loss (CVL) watch television, videos and movies, but often report difficulty and have reduced video comprehension. An approach to assist viewing videos is electronic magnification of the video itself, such as Bubble Magnification. METHODS: We created a Bubble Magnification technique that displayed a magnified segment around the centre of interest (COI) as determined by the gaze of participants with normal vision. The 15 participants with CVL viewed video clips shown with 2× and 3× Bubble Magnification, and unedited. We measured video comprehension and gaze coherence. RESULTS: Video comprehension was significantly worse with both 2× (p = 0.01) and 3× Bubble Magnification (p < 0.001) than the unedited video. There was no difference in gaze coherence across conditions (p ≥ 0.58). This was unexpected because we expected a benefit in both video comprehension and gaze coherence. This initial attempt to implement the Bubble Magnification method had flaws that probably reduced its effectiveness. CONCLUSIONS: In the future, we propose alternative implementations of Bubble Magnification, such as variable magnification and bubble size. This study is a first step in the development of an intelligent-magnification approach to providing a vision rehabilitation aid to assist people with CVL.
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Dahrouj M, Miller JB. Artificial Intelligence (AI) and Retinal Optical Coherence Tomography (OCT). Semin Ophthalmol 2021;:1-5.Abstract
Ophthalmology has been at the forefront of medical specialties adopting artificial intelligence. This is primarily due to the "image-centric" nature of the field. Thanks to the abundance of patients' OCT scans, analysis of OCT imaging has greatly benefited from artificial intelligence to expand patient screening and facilitate clinical decision-making.In this review, we define the concepts of artificial intelligence, machine learning, and deep learning and how different artificial intelligence algorithms have been applied in OCT image analysis for disease screening, diagnosis, management, and prognosis.Finally, we address some of the challenges and limitations that might affect the incorporation of artificial intelligence in ophthalmology. These limitations mainly revolve around the quality and accuracy of datasets used in the algorithms and their generalizability, false negatives, and the cultural challenges around the adoption of the technology.
Di Zazzo A, Gaudenzi D, Yin J, Coassin M, Fernandes M, Dana R, Bonini S. Corneal angiogenic privilege and its failure. Exp Eye Res 2021;204:108457.Abstract
The cornea actively maintains its own avascular status to preserve its ultimate optical function. This corneal avascular state is also defined as "corneal angiogenic privilege", which results from a critical and sensitive balance between anti-angiogenic and pro-angiogenic mechanisms. In our review, we aim to explore the complex equilibrium among multiple mediators which prevents neovascularization in the resting cornea, as well as to unveil the evolutive process which leads to corneal angiogenesis in response to different injuries.
Dobry A, Begaj T, Mengistu K, Sinha S, Droms R, Dunlap R, Wu D, Adhami K, Stavert R. Implementation and Impact of a Store-and-Forward Teledermatology Platform in an Urban Academic Safety-Net Health Care System. Telemed J E Health 2021;27(3):308-315.Abstract
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Dohlman TH, Singh RB, Dana R. Advances in the Medical Management of Neurotrophic Keratitis. Semin Ophthalmol 2021;:1-6.Abstract
Neurotrophic Keratitis (NK) is a degenerative disorder of the cornea characterized by decreased or absent sensory corneal innervation, corneal epitheliopathy and impaired healing.The clinical presentation of NK can range from persistent epithelial defects to corneal perforation and management is often both challenging and protracted. Historically, the management of NK has consisted of non-specific strategies to facilitate corneal epithelial healing such as lubrication, bandage contact lenses and tarsorrhaphy. Recent advances in the development of therapeutics for NK have provided new and efficacious targeted strategies for its management.In this article, we review recombinant human nerve growth factor (Cenegermin), currently approved for clinical use in the United States and Europe, as well as other promising therapeutic options that are in pre-clinical development such as thymosine β4, connexin43 inhibitors, and artificial extracellular matrix components.
Douglas VP, Douglas KA, Rapalino O, Champion SN, Chwalisz BK. Nelson Syndrome: Clival Invasion of Corticotroph Pituitary Adenoma Resulting in Alternating Sixth Nerve Palsies. J Neuroophthalmol 2021;41(1):114-118.Abstract
ABSTRACT: A 44-year-old woman presented with 2 painful and self-limited episodes of binocular horizontal diplopia within 1 year that at the beginning were thought to be secondary to microvascular insult. Her medical history was significant for Cushing syndrome status post transsphenoidal resection with bilateral adrenalectomy 4 years prior, hypertension, and diabetes mellitus. Neuro-ophthalmic evaluation was significant for left abduction deficit and incomitant esotropia consistent with left abducens nerve palsy. Of note, the patient had experienced a similar episode but on the contralateral side a few months prior. Although initially MRI of the brain demonstrated stable residual postoperative finding in the sella, upon review, an heterogenous T-1 hypointense marrow in the clivus was noted. Hypermetabolism of the clivus was also noted on computed tomography positron emission tomography of the skull base. A clival biopsy demonstrated a corticotroph adenoma with elevated proliferation index and scattered mitoses. A corticotroph pituitary adenoma after adrenalectomy, also known as Nelson syndrome, was diagnosed. Radiation therapy was offered to the patient, and resolution of symptoms was gradually observed.

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